The greatest obstacle impeding the progress of research on slow brain infection in humans and animals has been the inability to characterize the transmissible agent responsible for these infections. Recently, an electron microscopic study of Creutzfeldt-Jakob disease revealed inclusions presenting morphological characteristics similar to that of Spiroplasma, a plant and insect pathogen. Studies have also shown that Spiroplasmas are capable of producing experimental slow brain infection in suckling rats. However, little data has evolved from these studies related to the mechanisms of Spiroplasma infection in this vertebrate model. A preliminary study has shown a spongiform encephalopathy akin to that of Creutzfeldt-Jakob disease or Scrapie. This study has indicated that unequivocal identification of Spiroplasma can only be demonstrated by a more sophisticated approach, such as immunocytochemistry. This proposal will be structured to correlate the morphology and location of the Spiroplasma organism within the infected rat brain tissues with histologic changes and time relationship employing immunocytochemical methodology. At the same time the study will compare the neuropathology associated with Scrapie infection in a similar rat model referred to above. Search will also be made of Creutzfeldt-Jakob diseased and Scrapie diseased brains for Spiroplasma-related antigen. An attempt will be made to culture Spiroplasma on special broth directly from the diseased human and animal tissues. The study will hopefully provide an immunologic marker of Spiroplasma infection in Creutzfeldt-Jakob disease.